Ethical review of COVID-19 vaccination requirements for transplant center staff and patients.

Transplant centers seeking to increase coronavirus disease 2019 (COVID-19) vaccine coverage may consider requiring vaccination for healthcare workers or for candidates. The authors summarize current data to inform an ethical analysis of the harms, benefits, and individual and societal impact of mandatory vaccination, concluding that vaccine requirements for healthcare workers and transplant candidates are ethically justified by beneficence, net utility, and fiduciary duty to patients and public health. Implementation strategies should mitigate concerns about respect for autonomy and transparency for both groups. We clarify how the same arguments might be applied to related questions of caregiver vaccination, allocation of other healthcare resources, and mandates for non-COVID-19 vaccines. Finally, we call for effort to achieve global equity in vaccination as soon as possible.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Health-related quality of life and associated factors in HIV-positive transplant candidates and recipients from a HIV-positive donor.

INTRODUCTION: HRQOL in transplant candidates and recipients who are also infected with HIV and are awaiting a kidney, or have received one from a HIV-positive donor, has not been previously investigated. METHODS: The HRQOL of 47 HIV-positive kidney transplant candidates and 21 recipients from HIV-positive donors was evaluated using the Short Form-36 (SF-36) and face to face interviews at baseline and at 6 months. The correlation between SF-36 scores and sociodemographic, clinical and nutritional factors was determined. RESULTS: 68 patients completed the SF-36 at baseline and 6 months. Transplant candidates: transplant candidates had lower HRQOL than recipients. The main mental stressors were income, employment and waiting for a donor. Physical health complaints were body pain (BP) and fatigue. Pre-albumin and BMI was positively correlated with general health at baseline (r = 0.401, p = 0.031 and r = 0.338, p = 0.025). Besides a positive association with role physical (RP) and BP, albumin was associated with overall physical composite score (PCS) (r = 0.329, p = 0.024) at 6 months. Transplant recipients: Transplant recipients had high HRQOL scores in all domains. PCS was 53.8 ± 10.0 and 56.6 ± 6.5 at baseline and 6 months respectively. MCS was 51.3 ± 11.5 and 54.2 ± 8.5 at baseline and 6 months respectively. Albumin correlated positively with PCS (r = 0.464, p = 0.034) at 6 months and role emotional (RE) (r = 0.492, p = 0.024). Higher pre-albumin was associated with better RE and RP abilities and MCS (r = 0.495, p = 0.034). MAMC was associated with four domains of physical health and strongly correlated with PCS (r = 0.821, p = 0.000). CONCLUSION: Strategies to improve HRQOL include ongoing social support, assistance with employment issues and optimising nutritional status.

A prospective multicenter pilot study of HIV-positive deceased donor to HIV-positive recipient kidney transplantation: HOPE in action.

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

Strategic plan for integrated care of patients with kidney failure.

There is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5-10 years.

HIV-Positive Kidney Donor Selection for HIV-Positive Transplant Recipients.

The risks associated with transplanting HIV-positive kidneys into HIV-positive recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV-positive deceased donors have been transplanted into patients who are HIV positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to trauma. The average age for donors was 34 (interquartile range, 19-52) years old. In some donors, only one kidney was used because of a limited number of suitable recipients on the waiting list. Only two donors had been previously exposed to antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status was not known before the time of death. Initial concerns about transplanting HIV-positive allografts into HIV-positive recipients in this clinic revolved around the possibility of HIV superinfection. However, all recipients remained virally suppressed several years after the transplant. Only one recipient experienced an increased viral load after the transplant, which was related to a period of noncompliance on her medication. After counseling and improved compliance, the viral load decreased and became suppressed again. Herein, we discuss the findings of this study and review the literature available on this crucial topic.

HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years.

BACKGROUND: The outcome of kidney transplantation in human immunodeficiency virus (HIV)-positive patients who receive organs from HIV-negative donors has been reported to be similar to the outcome in HIV-negative recipients. We report the outcomes at 3 to 5 years in HIV-positive patients who received kidneys from HIV-positive deceased donors. METHODS: We conducted a prospective, nonrandomized study of kidney transplantation in HIV-infected patients who had a CD4 T-cell count of 200 per cubic millimeter or higher and an undetectable plasma HIV RNA level. All the patients were receiving antiretroviral therapy (ART). The patients received kidneys from deceased donors who tested positive for HIV with the use of fourth-generation enzyme-linked immunosorbent assay at the time of referral. All the donors either had received no ART previously or had received only first-line ART. RESULTS: From September 2008 through February 2014, a total of 27 HIV-positive patients underwent kidney transplantation. Survivors were followed for a median of 2.4 years. The rate of survival among the patients was 84% at 1 year, 84% at 3 years, and 74% at 5 years. The corresponding rates of graft survival were 93%, 84%, and 84%. (If a patient died with a functioning graft, the calculation was performed as if the graft had survived.) Rejection rates were 8% at 1 year and 22% at 3 years. HIV infection remained well controlled, with undetectable virus in blood after the transplantation. CONCLUSIONS: Kidney transplantation from an HIV-positive donor appears to be an additional treatment option for HIV-infected patients requiring renal-replacement therapy. (Funded by Sanofi South Africa and the Roche Organ Transplantation Research Foundation.).

Urological complications following unstented pediatric renal transplantation.

Urological complications which develop post-renal transplantation can be associated with significant morbidity especially in children. We evaluated the occurrence and management of all urological complications in a series of unstented pediatric renal transplants in a tertiary pediatric hospital. We reviewed the medical records of children who underwent unstented renal transplant between January 1996 and December 2014. Postoperative urological complications and the outcomes of their management were analyzed. A total of 160 unstented renal transplants were performed, and 32 urological complications were noted in 29 transplants (18%). There were 20 boys and nine girls with an age range of 2.5 years to 18.4 years. Nine (31%) of these patients had LUTD. The most common complication was VUR occurring in 17 patients (10.6%). Urine leaks occurred in six patients (3.8%) and ureteric obstruction in six patients (3.8%), and three patients (1.9%) had unexplained hydronephrosis. Loss of graft occurred in three patients (1.9%), and one patient died from sepsis post-uretero-ureterostomy. Patients with LUTD had more urological complications (P = .037). Unstenting is feasible in most pediatric renal transplants. LUTD is associated with a higher incidence of urological complications, especially VUR.

Transplantation in Africa - an overview.

Africa is underdeveloped in terms of treatment options for patients with end-stage renal failure. Economic growth and corresponding increases in health expenditures in the African region mean that we can confidently anticipate increased demand for organ transplantation within the region over the next few years. Renal failure in Africa occurs mainly due to glomerular nephropathies, hypertension, diabetes, and HIV. For the subset of the population that might be considered medically suitable for transplantation, demand for transplantation is tightly constrained by the availability of specialist physicians and surgeons, pathology facilities, capacity to achieve acceptable graft outcomes, cultural and religious attitudes towards organ donation, trust in the health system, and the extent to which patients are able to meet the costs of surgery and ongoing immunosuppression. There are currently several countries in Africa which are building up living-related-donor transplantation. Active living-donor transplantation already takes place in South Africa, Tunisia, and Sudan, but deceased donation is only available in South Africa. Whereas living-donor transplantation might be successfully driven by a motivated individual and a single institution, deceased-donor transplantation requires dialysis programs, tissue typing and crossmatching facilities, an organ procurement program, an on-call surgical team, capacity to fund this infrastructure, and an appropriate legislative framework. A significant and recurring barrier to transplantation in the African region is the high cost of transplantation and follow-up care, and, in particular, the cost of maintenance immunosuppression. A positive environment that could potentially change this scenario will have to include governmental funding, academic support to clinicians as well as a legislative framework, which is still needed in many African countries.

Transplantation in resource-limited setting: using HIV-positive donors for HIV-positive patients.

BACKGROUND: A HIV positive-to-positive program was started in South Africa in 2008. The program was started because dialysis is not freely available to everyone, but severely limited and only available to a selected group of patients. PATIENTS AND METHODS: Between September 2008 and March 2015, 29 patients were transplanted from HIV-positive brain-dead donors at Groote Schuur Hospital transplant team. Donors were either naïve to anti-retroviral therapy or on first line therapy. The recipients were selected to have undetectable plasma HIV type 1 RNA levels and be on a stable antiretroviral regimen. CD4+ T-cell counts of at least 200/mm3 in last 6 months prior to transplant, with no previous serious opportunistic infections. RESULTS: Survivors in the study were followed for a median of 2.4 years. The rate of patient survival was 84% at 1 year and 74% at 5 years. The corresponding graft survival rate was 93% and 84%. CONCLUSION: Using HIV-positive donors might resolve some of the problems we are experiencing in getting enough donors for our patients wit ESRD. In the USA the HOPE act was accepted in 2014 and this might now also impact on the use of HIV positive donors elsewhere in the world.

Transplant commercialism and organ trafficking: the Declaration of Istanbul with special relevance to disadvantaged populations living with kidney disease.

This paper provides a historical perspective on organ trafficking and transplant commercialism, an overview of the Declaration of Istanbul [1, 2], and an update on current state. We highlight the importance of this problem pertaining to disadvantaged populations living with or at risk for kidney disease. It was presented during the Kidney Disease in Disadvantaged Populations Satellite Symposium of the World Congress of Nephrology in Hong Kong 2013 (www.theisn.org).

Laparoscopic kidney donation - giving in the best way possible.

Laparoscopic donor nephrectomy is the preferred method of living kidney donation at most transplant centres. There are various techniques, all with their own reported benefits. This editorial gives a brief overview of the various methods in the context of ensuring maximum safety and benefit to the donor without compromising kidney transplant outcomes.

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement.

Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.

Attitudes and beliefs of South African medical students toward organ transplantation.

The aim of this study was to assess and analyse the attitudes and beliefs of medical students regarding organ donation, procurement, and transplantation. Medical students at the University of Cape Town were prospectively surveyed using a self-administered questionnaire. There were 346 study participants; the mean age was 21 (range 18-33) yr, 38% were male and 62% was female. Only 8% of respondents were registered donors; clinical and white students constituted the majority of this group. Of the 315 "non-donors," the main reason for not donating was "I have not really thought about organ donation" (59%). Most students (91%) would accept an artificial organ; and 87% and 52% of students would accept human and animal organs respectively. Muslim students (11%, p<0.05) and those who believe in an after-life or reincarnation (18%, p=0.00) were less willing to accept human or animal organs. About 95% of respondents stated that they would like to learn more about transplantation and would keep information about it in their practice but only 18% of respondents knew where to find information for potential donors and recipients. Most students have a favorable attitude toward organ transplantation; religion and belief systems impact on willingness to receive organs.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients.

Introduction: The management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited. Methods: This retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression. Results: There were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03-7.48), P = 0.044). Conclusion: Despite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.